Anticoagulant Drugs 11 to 20
Outline the clinical features of salicylate toxicity?
Prompt if required: What are the acid base disturbances in salicylate toxicity?
Any CNS: coma
Uncoupling Oxidative Phosphorylation
Describe the enhanced elimination strategies employed in managing a patient with salicylate overdose?
pH Manipulation /urinary alkalinisation
Prompt for both
NOTES: Dialysis procedures
1. Peritoneal dialysis
What are the preferred administration routes for Vitamin K?
Oral, im iv
NOTES: ORAL DOSE – Absorption is inconsistent
Rapid intravenous infusion may produce flushing, cyanosis, dizziness, hypotension, and bronchoconstriction.
What are the clinical indications for prescribing Vitamin K?
Reversal of oral anticoagulant effect Management of warfarin toxicity or superwarfarin toxicity (brodifacoum) Vit K defic
Prevention of haemorrhagic disease of the newborn
Treatment of haemorrhagic disease of the newborn
NOTES: ORAL VITAMIN may be indicated in small ingestions or when the amount is uncertain, but presumed to be small.
INTRAVENOUS VITAMIN K
INDICATIONS – Intravenous phytonadione is preferable in SEVERE cases where rapid correction is required. Adults: A minimum of 10 mg IV diluted in saline or glucose at a rate not exceeding 5 percent of the total dose per minute. In maximally anticoagulated individuals, repeat doses at 6-8 hour intervals
Describe the mechanism of action of clopidogrel.
Irreversibly blocks the ADP receptor on platelets to inhibit platelet aggregation.
How does it differ from aspirin?
Asprin inhibits the synthesis of Thromboxane A2 within platelets by the irreversible acetylation of cyclooxygenase. (1 of 2)
NOTES: Thienopyridine derivative. Unlike asprin has no effect on PG metabolism
What other types of anti-platelet agents are there?
Phosphodiesterase inhibitors (dypridamole)
Glycoprotein 11b/l la inhibitors (abciximab) (1 of 2)
How does heparin act?
- Heparin binds endogenous antithrombin and enhances its activity.
- Antithrombin inhibits factors IIa, IXa and Xa by complexing with them and inducing a conformational change.
- Bold to pass
How may heparin be administered?
- IV vs SC
- Continuously (following bolus) vs intermittent
- Therapeutic vs prophylactically
- Bold to pass
What are the potential adverse effects of heparin?
- Heparin-induced thrombocytopaenia
- Mineralocorticoid deficiency
- Bold +1 to pass
What are the advantages of low molecular weight heparins compared to unfractionated heparin?
- Have equal efficacy
- Increased SC bioavailability
- Require less frequent dosing
- Less monitoring
- Shorter chain heparin with less effect on thrombin (IIa)
- Demonstrates understanding
What methods are available to reverse warfarin induced anti-coagulation?
- Cease warfarin
- Vitamin K – oral or IV 1-10mg
- +/- fresh frozen plasma or prothrombinex
- 2/3 bold to pass, must include vitamin K
How does vitamin K reverse warfarin effect?
- Pharmacodynamic interaction with warfarin to reduce INR i.e. reverses the effect of warfarin
- Re-establishes normal activity of the clotting factors. Vitamin K dependent clotting factors: II, VII, IX, X
- Bold to pass
How long does it take for vitamin K to work?
- 6-24 hours
- >6 hours
What is vitamin K?
- Fat-soluble substance in leafy vegetables
- Usually synthesized by gut bacteria
- Vit K1 (food)
- Vit K2 (bacteria)
- Bold to pass
Please describe its mechanism of action in reversal of warfarin on anticoagulation
Prompt: How long does it take for the onset of action?
- Coumarin anticoagulant
- Prevents reductive metabolism of inactive vit K to active form
- Produces biologically inactive VII, IX, X, prothrombin, protein C & S
- Vit K1
- Confers biologic activity upon prothrombin and factors VII, IX, X by participating in their postribosomal modification
- Onset of action 6 hours, complete by 24 hours
- To pass need concept of warfarin producing biologically inactive factors, vit K overcoming this, and delayed onset of action
Describe the mechanism of action of rivaroxaban.
Inhibits both free and prothrombinase-bound forms of activated factor X.
- Inhibits factor Xa.
Describe the pharmacokinetics of rivaroxaban.
- Oral bioavailability >80%
- Maximal plasma levels 3 hours post ingestion
- Small volumes of distribution (<50L)
- Highly protein bound
- Elimination is predominantly renal and hepatic (CYP3A4) with steady state half0life of 5-14 hours
- Half-life is prolonged with renal impairment
- 2 things including predominant renal excretion to pass.
What clinical advantages does rivaroxaban offer over warfarin?
- More rapid onset/offset of action
- More predictable effect – easier dosing, with a wider therapeutic index
- INR monitoring not required
- Fewer drug and dietary interactions
- 2 to pass. Better candidates will be able to correlate differing MOA and pharmacokinetics to advantages.
Extra question: Do the pharmacokinetics of rivaroxaban present any clinical disadvantages relative to warfarin?
Predominant renal excretion means that doses must be adjusted in renal failure, and it is not suitable for dialysis patients.
- Supplementary question. Only used if there is sufficient time. No specific pass criteria.